It is proposed to study enzymes isolated from Clostridium thermoaceticum and Clostriduum formicoaceticum. The enzymes catalyze the conversion of one-carbon derivatives of vitamin-B12 and folic acid. The compounds are intermediates in the synthesis of acetate from CO2. Specifically we will study formyltetrahydrofolate synthetase and methylenetetrahydrofolate dehydrogenase. Investigations will be done regarding the structure, such as subunits and their interaction with both enzymes and also of the kinetics of the latter. A third enzyme, formate dehydrogenase, which reduces carbon dioxide to formate using NADPH will be investigated. It contains selenium and tungsten, and the role of these metals in the enzyme will be studied and attempts will be made to purify it although it is strongly inhibited by oxygen and requires work under strictly anaerobic conditions. Evidence has accumulated that the reduction of carbon dioxide to acetate is coupled with electron transport phosphorylation. This will be investigated and electron carriers, such as cytochromes, non-heme proteins and B12-proteins, will be isolated.